Project Summary/Abstract Neuroscience research over the last decade has been revolutionized by many technological advancements. Pharmacology and optogenetics represent two distinct, and sometimes complementary tools used in neuroscience research to study the central and peripheral nervous systems in the context of the BRAIN initiative. Advanced interrogations of underlying neural circuits and biology are often frustrated, however, by technological limitations that prevent the use of these approaches to study natural behaviors of untethered, freely moving animals. Traditional fiber-optic cable for optogenetics and bulky metal cannulas connected with external mechanical pumps for pharmacology impart significant damage to fragile neural tissue, limit the natural behavior of freely moving animals, affect social interactions and movements in complex, naturalistic 3D environment, and lead to persistent irritation at the biotic/abiotic interface due to mechanical mismatch and micromotions. These drawbacks, together with the costly setup, of current technologies motivate the development of innovative engineering designs to improve fidelity, operational ease, versatility and range of advanced brain research studies with live animal models. Our work during Phase I developed an integrated, wireless platform that combines capabilities in programmable pharmacology via soft ?-fluidic channels and optogenetics through an implantable ?-scale inorganic light emitting diodes (?-ILEDs). The proposed work for Phase II focuses on translational engineering research to refine the device designs and to develop a low-cost, mass-manufacturing process. Specifically, the proposed work will (1) establish device designs, and manufacturing process for low-cost, outsourced production, (2) expand the functionality for directly interfacing with peripheral nerve and spinal cord, and (3) develop advanced capabilities in power harvesting, modulation, and control, and broaden the impact on neuroscience research. This work will yield a broadly useful, low-cost, wireless platforms for programmable pharmacology and optogenetics in various contexts of essential relevance to the BRAIN initiative.